Tezepelumab 210mg/1.91ml solution for injection pre-filled disposable devices

Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.

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A 38-year-old man with near fatal asthma requiring intubation and invasive mechanical ventilation (IMV) was transferred to our hospital. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated due to hypotension and mediastinal emphysema secondary to barotrauma. Since high-dose systemic corticosteroid therapy failed to relieve the severe bronchospasm, a single dose of tezepelumab was administered on a compassionate basis. This intervention resulted in successful extubation 7 days later. This is a rare case in which a biologic agent was used as a rescue therapy for near fatal asthma. This case is presented along with a review of the relevant literature.

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Background In asthma, clinical response is characterised by disease improvement with treatment, whereas clinical remission is characterised by long-term disease stabilisation with or without ongoing treatment. The proportions of patients receiving tezepelumab who responded to treatment and who achieved on-treatment clinical remission were assessed in the NAVIGATOR (ClinicalTrials.gov identifier NCT03347279 ) and DESTINATION (ClinicalTrials.gov identifier NCT03706079 ) studies of severe, uncontrolled asthma. Methods NAVIGATOR and DESTINATION were phase 3, randomised, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV 1 ) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physician's assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV 1 >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed. Results Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0–52 (46% versus 24%; OR 2.83, 95% CI 2.10–3.82) and on-treatment clinical remission over weeks 0–52 (28.5% versus 21.9%; OR 1.44, 95% CI 0.95–2.19) and weeks >52–104 (33.5% versus 26.7%; OR 1.44, 95% CI 0.97–2.14). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarker levels at baseline, and fewer exacerbations in the 12 months before the study. Conclusions Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes, but may be driven by different patient characteristics.

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INTRODUCTION: Tezepelumab is an anti-TSLP monoclonal antibody approved for the treatment of severe asthma. It has broad downstream anti-T2 effects, offering the prospect of biological remission. Real-world data on clinical remission rates with tezepelumab is lacking, and the relationship between clinical and biological remission is unclear. Finally, the effectiveness of tezepelumab in patients who have failed to respond to existing biologic therapies is unknown. METHODS: Clinical and biomarker data from adults with severe asthma treated with tezepelumab in a real-world setting was analyzed. Clinical outcome measures including clinical remission were recorded along with rates of biological remission (defined as blood eosinophil count < 300 cells/mcL and FeNO < 25 ppb). RESULTS: One hundred seventy-five patients were included. 98/175 (56%) had switched from another biologic. Following tezepelumab initiation, the exacerbation rate decreased from 3.1 (2.5) to 0.8 (1.4), with 59% of patients remaining exacerbation-free at 1 year. 54% achieved an ACQ score < 1.5. Clinical remission at 1 year was observed in 36%, with a rate of 55% in T2-high patients versus 19% in T2 low patients. The clinical response in biologic-naïve and biologic switch patients was similar. FeNO declined from 41 ppb (24-76) to 24 ppb (16-38) and BEC fell from 300 cells/μL (60-610) to 180 cells/μL (105-320) (both p < 0.001). 38% achieved biological remission. 15% attained both clinical and biological remission. CONCLUSION: Tezepelumab led to substantial clinical improvements and clinical remission in up to 55% of T2-high patients with severe asthma. A disconnect between clinical and biological remission was observed. The long-term significance of residual T2 inflammation on tezepelumab is unknown.

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